Patho Final Notes PDF

Cancer HIV ARO Covid Autoimmunity\* Hypersensitivity Influenza Immunity AIR Viruses Cancer 2/5 Canadians are expected to develop cancer in their lifetime Most common types of cancer- lung, prostate, breast and correctal Most common childhood cancer is leukemia Definitions: neoplasms:...

Cancer HIV ARO Covid Autoimmunity\* Hypersensitivity Influenza Immunity AIR Viruses Cancer 2/5 Canadians are expected to develop cancer in their lifetime Most common types of cancer- lung, prostate, breast and correctal Most common childhood cancer is leukemia Definitions: neoplasms: new growth Anaplasia: absence of differentiation Cancer: refers to a malignant tumor and is not a term used to refer to benign growths Carcinogen: substances that when introduced into a cell, cause changes in the structure and function of the cell and lead to cancer Carcinogenesis: production of cancer Leukemia: Cancers from blood forming cells (ex. WBC) Oncogenesis: the production or causation of cancer Proto- oncogene: is a normal gene that promotes cell growth (ex. Turns of cell division) Oncogene: is made from a mutated proto-oncogene that now results in excessive and uncontrolled cel growth Tumor suppressor gene: inhibits cell replication Differences between benign and malignant neoplasms Does not metastasis Can metastasize --------------------------------------------------------------------------- ----------------------------------------------- Does not usually cause symptoms unless the location interrupts blood flow Causes symptoms: weight loss, fatigue, anemia Encapsulates and doesn't infiltrate surround tissue Infiltrates and destroys surrounding tissue Slow growing Fast growing Doesn't usually cause death Can cause death If removed does not usually reoccur Often reoccurs after removal Oncogenesis: production of cancer What are 2 classes of genes, that when mutated, play the biggest role in uncontrolled cell proliferation seen in cancer? Proto-oncogenes and Tumor suppressor genes How many 'hits' for a normal cell to transform to a cancer cell? 4-7 hits What are the different types of 'hits' or carcinogens? 1. Hormonal- too much estrogen, going through menopause (lower estrogen), PCOS 2. Environmental- air pollution, water pollution, asbestos, power lines 3. Occupational- welders, nail techs/aestheticians, nurses, firefighters, farming, factory workers 4. Viruses- HPV, hepatitis B, herpes, Epstein Bar virus 5. Behavioral- smoking, drinking, unsafe sex, sun exposure 6. Other factors- genetics, diet, age How does gene mutation occur? 1. **Point Mutation-** a single change to one base group (switch one base for another base- switch a A with a G)- change 1 letter 2. **Frame shift mutation-** adding or deleting a letter (this messes up the codon and it no longer makes sense- it changes the way it is read) 3. **Chromosome translocation-** a piece of one chromosome is translocated to another chromosome (ex of this is Burkitts lymphoma) 4. **Gene amplification-** duplication of a small piece of chromosome over and over again. Instead of 2 copies of the gene you have 10-100 (an example of this is Human epidermal growth factor (HER2) breast cancer What factor contribute to gene mutation? 1. **Hereditary genetic errors passed on from parents to their offspring** a. **Autosomal dominant inheritance**- -there are no carriers of autosomal dominant disorders- a person is either affected or not affected (affected does not mean you will get cancer it just means your risk is higher. You only need one copy of the allele M= affected N= unaffected b. Autosomal recessive inheritance - There can be carriers so you can pass it on to offspring and not be affected. It takes both alleles to be affected tho. If you come from the same ancestors theres a higher chance (consanguineous) 2. Exposure to a carcinogen: ones talked abt above 3. Exposure to a virus: EBV, HPV, Human t cell leukemia virus, Hep b How does cancer arise? - Proto-oncogenes being mutated- turns into oncogene=cancer - Safeguard systems failing: tumor suppressor gene mutation, a mismatch in gene repair, failure of apoptosis and immune system dysfunction How does a proto- oncogene become an oncogene? - Proto-oncogenes promote cell growth and development. When proto-oncogenes become damaged they mutate and become oncogenes (cancer). The oncogenes flood the cells with signals to inappropriately divide which is bad=tumor growth - Ex. Like a gas pedal being pushed down even when the persons foot isn't on the pedal How does inactivation of tumor suppressor gene contribute to cancer growth? - The normal function of TSG is to inhibit cell growth. When the gene is inactivated then we cant stop inappropriate cell growth - TSG has 2 alleles and you need both to be damaged for this to happen. If both TSG are mutated or damaged then we lose the ability to inhibit cell growth - Retinoblastoma is a common cancer that is cause by damaged TSG How does inactivation of the mismatched repair gene contribute to cancer growth? - The mismatch repair genes function is to repair errors that occur during DNA replication. Its like a spell checker. Damage to the MRG is usually from environmental factors such as smoking How does failure of apoptosis contribute to cancer growth? - Normally damaged cells self apoptosis. However with failure of apoptosis old cells reach life expectancy and don't apoptosis. The old cells will them replicate which is really bad bc we don't want old cells aking copies bc they aren't very healthy and have a higher chance of mutation How does immune dysfunction contribute to cancer growth? - It has the ability to outpace the immune system and it doubles the speed of replication - If the immune system isn't working properly cancers can display MHC 1 (self) and then the immune system wont destroy the cancer cells - In immune system dysfunction we lose contact inhibition (ex. Cancer cells in the kidney will tell other kidney cells it is not mutation and can hide out undetected even by surrounding cells) What are the local manifestations of cancer (symptoms)? -local manifestations depend on where the tumor is located. For example a tumor in the prostate may cause difficulty urination due to the tumor pressing up against the urethra \- tumors in smaller areas will show local manifestations sooner than tumors in larger areas. This is why we see symptoms from prostate cancer sooner than the stomach (prostate is smaller than stomach) \- symptoms also depends on the surrounding structures. For example a tumor by a bone could cause bone pain from the tumor pressing up against the bone When do we see systemic manifestations of cancer? - If it metastisizes Pathophysiology of tumor spread 1. Transformation of an individual cell 2. Growth of the transformed cell 3. Local tissue invasion- mechanical pressure, release of lytic enzymes, motility of the cancer cells 4. Dissemination 5. Establishment of a new site (metastasis HIV How is HIV transmitted? - It is transmitted through exposure to bodily fluids 1. Sexual contact- anal sex (higher risk bc if higher damage during sex) vaginal sex (women 13-25 are more at risk bc of an immature genital tract mucosa), oral sex (lower risk but a cut in the mouth could do it) 2. Blood contact- sharing needles, exposure to blood through cuts, transfusions 3. Mother to child transmittion -- this is higher in developing countries. It can be passed on during pregnancy, during delivery and while breastfeeding What factors increase risk of mother passing on HIV to baby? - If the mother contracts HIV just before pregnancy than the risk is higher bc in the beginning stages of HIV is when you have the highest viral load - Breast feeding habit can increase risk. You want to instruct a mother to either exclusively breast feed or exclusively bottle feed. DO NOT SWITCH BACK AND FORTH. This is because switching can damage the infants gut which increases risk (bc remember it needs to enter the blood stream- stomach is fine if it isn't damaged). - If the mom has oral or breast leasions it increases the risk of transmittion - Having a C section or using forceps suring delivery can increase chance of trasmittion to baby due to risk of blood mixing Do ARTs reduce chance of transmitting HIV to baby? YES If you had a mother living in northern BC that has has HIV would you formula feed or breast feed? You would want to recommend exclusively breast feeding because there is less access to formula and we don't want to switch back and forth. This would be the same for low income families. If you have a mother who can afford to formula feed and has access to formula then recommend that. Who is more at risk? Insertive or receptive? Receptive bc they are more likely to get micro tears What bodily fluids can transmit HIV? - Blood - Semen - Pre-ejaculate - Vaginal secretions - Breast milk What bodily fluids can not transmit HIV? - Tears - Sweat - Vomit - Feces - Urine What are the different types of HIV? HIV 1- has lots of mutations or clades bc it has a rapid rate of ( HIV 2- les errors, slower to replicate, less virulent and doesn't have any clades (west Africa) What is the function of Reverse transcriptase in HIV? It converts RNA to DNA What are the main targets of HIV? T helper cells, macrophages, dendritic cells and microglia (in CNS) and anything with a CD4 receptor- bc HIV requires a CD4 receptor to initially bind to the T helper cell and macrophages HIV must also bind with a coreceptor (ex xytokines). The GP120 (gylcoproteins bind to the CD4 cells on the host) \*HIV can hide out in the CNS bc our immune system cant cross the BBB What co receptor will we see in early stages of HIV? CCR5 on macrophaes And in late stages of HIV? -CXCR4 on T helper cells Why is CD4 testing helpful in HIV? It helps determine the degree of immunocompromise. Explain viral set point - This is where different people are at with their viral load after the initial few weeks of high viral load. Not everyone will have crazy high viral loads after this time. People with a high viral set points after the acute phase should be started on antiretrovirals immediately Explain the phases of HIV infection? 1. Acute primary HIV infection phase -- 1^st^ 6-8 wks -- highest viral load - Signs and symptoms of acute HIV infection usually occur 10-25 days after exposure. Usually lasts 1-2 weeks - Fever, myalgia, fatigue, sore throat, headache, night sweats, lymphadenopathy, skin rash - This is when you are most contagious 2. Acute HIV infection (seroconversion illness) 6 weeks we start seeing seroconverted antibodies. Before this time the only diagnostic would be looking at viral load. In stage 1 the macrophages present HIV antigens to CD4 cells which trigger B cells to make antibodies- this is what seroconversion means - Lasts 3 weeks -- 3 months 3. Chronic asymptomatic or latency phase - No signs or symptoms of illness - Phase usually lasts 10 years - Viral load is stable- for every 1 HIV virus destroyed 1 is replicated - CD4 counts will drop 50-90 cells per year (we start treatment in stage 2) 4. Overt aids phase - CD4 count is less than 200 cells - Typically ppl are experiencing weightloss, secondary neoplasms (cancers) and wasting syndrome Once you are detected for HIV you then go for monitoring Q3-4 months for CD4 counts Meds for HIV (ART) 1. Fusion inhibitor - Prevents virus from entering host cell CD4 cells(like a lock on factory door) 2. Protease inhibitors - Blocks protease inhibitors - Viral assembly is blocked (workers stop building the virus on the factory assembly) 3. NRTIs - Blocks the process of reverse transcription 4. NNRTIs or nonnukes - Binds directly to reverse transcriptase which prevents the conversion of RNA to DNA 5. Integrase inhibitor - Stops transfer of viral DNA into host DNA 6. CCR5 antagonist - Prevents fusion of virus and host cell membrane Failure of art therapy may be due to  Incomplete of adherence  Poor absorption  Toxicity/SE - lowered or missed doses by pts if they are having many SE  Pharmokinetic interactions or pharmacogenetic circumstances  Infected with a resistant virus Covid Structure - Spike proteins- responsible for recognition, attachment and fusion - Hemagglutinin esterase protein - Envelope bilayer- gives it structure and holds everything - Nucleocapsid protein- holds single strand of RNA - RNA (single strand) - M protein (membrane protein)- assembly and budding, neutralize antibodies - E protein (envelope protein) assembly and budding Reproductive ratio: for 1 infected individual how many people can it be passed on to (in Canada it is 0.91) Series interval: the time it takes to pass the virus on to another individual (Canada is 5.2 days) How is covid Transmitted?